PREVENTION OF HYPERACUTE REJECTION IN AN EX-VIVO PIG TO HUMAN CARDIAC XENOGRAFT

预防离体猪对人心脏异种移植物的超急性排斥反应

• 批准号: 6245181
• 负责人: Jonathan P Fryer
• 金额: $ 1.2万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-15 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6245181
• 关键词: binding proteins; cardiovascular transplantation; complement pathway; disease /disorder prevention /control; human tissue; perfusion; swine; synthetic peptide; transplant rejection; xenotransplantation

Because of the severe shortage of available human organs for donations, other species have been considered as potential donors for human transplantation. Of the options available the pig appears to be the most suitable candidates. Hyperacute rejections has been a major barrier to pig-to-human transplantation, although several strategies have been successful in preventing this. Despite preventing hyperacute rejection, delayed xenografic rejection occurs which is characterized by endothelial cell activation and invasion of macrophages and natural killer cells. Although many of the successful strategies to avert hyperacute rejection have used approaches which prevent complete activation of the complement cascade, none have attempted to inhibit the complement cascade in its earliest phases. Deposition of the initial components of the complement cascade (c1, c4, c2) can lead to the accumulation of inflammatory cells and may contribute to endothelial cell activation thus creating a situation which is consistent with delayed xenograft rejection. Using novel synthetic peptides (complementary binding peptides) developed at Northwestern University, we will attempt to block the deposition of the early components of the complement cascade, thus preventing hyperacute rejection as well as the pro-inflammatory stimulus which is elicited from these early components. This will be tested in an ex vivo perfusion circuit where human blood is perfused through a pig heart with and without the complementary binding peptides.

由于可供捐赠的人体器官严重短缺， 其他物种被认为是人类的潜在捐赠者 移植。在可用的选项中，猪似乎是 最合适的候选人。超急性排斥反应一直是一个主要障碍 到猪到人的移植，尽管有几种策略 成功地阻止了这种情况。尽管防止了超急性排斥反应， 以血管内皮细胞为特征的延迟性异种排斥反应 巨噬细胞和自然杀伤细胞的细胞活化和侵袭。 尽管许多成功的避免超急性排斥反应的策略 使用了阻止补体完全激活的方法 级联，但没有人尝试在其 最早的阶段。补语的初始成分的沉积 级联(c1、c4、c2)可导致炎症细胞积聚 并可能有助于内皮细胞的激活，从而创造一个 这种情况与延迟性异种移植排斥反应一致。vbl.使用 开发的新型合成肽(互补结合肽) 西北大学，我们将试图阻止沉积 补体的早期成分级联，从而防止超急性 拒绝以及由以下因素引发的促炎刺激 这些早期的组成部分。这将在体外灌流中进行测试 人体血液通过猪的心脏注入的回路 没有互补的结合肽。